Chapter:1 INTRODUCTION AND LITERATURE REVIEW
1. Schiff bases
A number of Schiff bases contain the imines function has been shown to has a wide
range of the biological activities the including antifungal ant diabetic antitumor ant
proliferative anticancer anticorrosive and anti inflammatory activities 1. The people are
working form last many years on the synthesis of characterization and the transition metal
complexes with the thissoemicarbazone because of their wide range medicinal of application
and their abilities to coordinate with the transition metal ions which is highly desirable the
Schiff bases has a chelating structure as demand because they are straight forward to prepare
and are moderate electron donor with easily tunable electronic and satiric effects the
synthesis and application of Schiff bases and their coordination compounds has been highly
considered in inorganic and bioinorganic field the since their structure properties similar to
some of the biological systems the many Schiff bases and their complexes has been widely
studied because of there are in the industrial and biological of the application the Schiff
bases compound (--RC=N--) are usually formed by the condensation of a primary amine
with an active of carbonyl the cross linking agents can also be derive form metal complexes
with O , N or S’ legends1.
Schiff bases of compound carrying imines or azome thine (-C=N-) function group
these are the condensation products of the primary amines with carbonyl compounds and
were first reported by hugo Schiff. The Schiff base form an importance class of the most
widely used organic compounds and has a wide variety of application in many fields
including analytical biological and inorganic chemistry Schiff base has gained importance in
medicinal and pharmaceutical filed due to broad spectrum of biological activities like anti-
inflammatory2.
Augmentation of biological activity was reported by the implementation of
transition metals into Schiff base. The Schiff bases played an influencing role in
development of coordination chemistry and were involved has key point in the development
by the inorganic and biochemistry and optical materials the Schiff bases has been utilized as
synthons in the preparation of a number of industrial and biologically active compounds
like Formosans the thiazolidines benzoxazines and so forthvia ring clodure cycloaddition
and replacement reactions the Schiff bases derivatives in various processes promoted the
researcher for designing of novel heterocyclic aryl Schiff bases for the development of the
new environmental friendly technology2.
A Schiff base named after Hugo Schiff is compound with the general structure
R1R2C=NR (R=H they can be considered a sub class 0f imines being either secondary
ketimines or secondary aldimines depending on their structure the term is often synomous
with azomethine which refers specifically to secondary aldimines i.e. . R-CH=NR where R
= H3 .
A number of special naming system exist for these c0mpounds. For instance a Schiff
bases derived form an aniline where R3 is a phenyl or a substituted phenyl can be called an
anil while bis- compounds are often referred to as salon type compounds. The Schiff bases
is normally applied to these compounds when they are being used as ligands to form of the
coordination with the metal ions. Such complexes occur naturally, for the catalysts such has
the Jacobsen’s catalyst3.
f igure 1.1 Genral structure of sciff base
2. History and background of Schiff bases
Hugo (Ugo) Schiff (1834-1915), a German scientist, was the inspiration for Schiff.
He discovered Schiff bases, as well as other imines, in 1864, and was liable for examination
in aldehydes, which were subjected to the Schiff test, which was named after him. Fuchsine
(appeared in Figure. 1.2) is concentrated for Schiff as a Schiff reagent in 1866, and became
widely used over the last several years of the nineteenth century of modern hues4.
Figure 1.2: 4,4'-((4-imino-3-methylcyclohexa-2,5-dien-1-ylidene) methylene) dianiline
hydrochloride.
A salen-type7 (shown in Figure.1.3) with a bifunctional and tetradentate (ONNO) ligand is a
remarkable Schiff base ligand. In 1985, R. Atkins proposed the name salen-sort of tetradentate
(ONNO) ligands to describe a few imbalanced salen type Schiff bases. Because the hydroxyl
groups in the ring are replaced, the 2-hydroxybenzaldehyde is an acceptable structural block.
When connected to metal atoms, this route of salen-type Schiff bases will form a steadier six-
part ring once the imine bond is fashioned from vital amine and aldehyde4.
Figure 1.3: (2,2'-((1E,1'E) -(ethane-1,2-diylbis(azanylylidene)) bis(methanylylidene)
3. Synthesis of Schiff bases by different methods;
Schiff bases are the important then intermediates for the synthesis of bioactive
compounds such has they are reported to show a variety of interesting the biological action
including antibacterial antifungal anti mouse hepatitis virus MHV inhibition of herpes
simplex virus the HSV and adenovirus 5.
It is also known that the presence of a chloral and an azo moiety in different types of
compounds can lead them to exhibit pesticidal activity some azo compounds synthesized by
jolly and coworkers have shown good antibacterial active 6.
In light of the interesting variety of biological activities seen in the compounds containing azo
methoxy groups and azomethine linkages it was thought of interest to examine the effect of
having all of the above functionalities present simultaneously in one the structure 7. based on
this notion we the decided to synthesize ten new azo Schiff bases and to test them against
staphylococcus aurous, bacillus subtitles’, kelebsiella pneumonia, pseudomonas aeruginosa and
Escherichia coli. The new azo Schiff bases were also tested against eight fungi including
Candida albicans. Cryptococus neoformans, tricophyton mentagrophytes, the aspergillus
fumigates, aspergullus niger and alternaria8
Development of non-hazardous synthetic methodologies for organic synthesis is one of the latest
challenges to organic chemists. The growing concern for the environment demands the
development of eco-friendly and economic processes wherein even less hazardous byproducts
are not desirable. Organic reactions under solvent-free conditions have gained in popularity in
recent years9
Since the majority of solvents are either toxic or flammable and add considerably to the cost of
an overall synthesis. These solvent-free reactions usually need shorter reaction times, simpler
reactors, resulting simpler and more efficient work up procedures, more improved selectivity and
easier separations and purifications than conventional solvents 10. The formation of carbon–
nitrogen double bond plays important role in organic synthesis. This can be achieved by the
reaction of aldehydes and amines in acidic medium which leads to synthesis of Schiff bases
(imines). Schiff bases have attracted considerable attention of organic chemists due to their
significant biological activities like anti-inflammatory agents11
Insecticidal, antibacterial, antituberculosis, antimicrobial, anticonvulsant 12. The Schiff bases are
also used as versatile components in nucleophilic addition with organ metallic reagents and in
cycloaddition reactions 13
6. Review of literature:
The imin group –N=CH- characterizes of the Schiff base this explaining of the
transformation and racemization mechanism in the biological system. The bio inorganic
chemistry is well as improve the concentration has the Schiff bases complexes. Because its
standard that is provide has various importance of the biological species. it can also be used as
pigments and colors, catalysts, intermediates in the organic synthesis and stabilizers in polymers.
The also used has pigments and paints, catalysts, intermediates in organic synthesis and
stabilizers in polymer imine metal complexes with the heterocyclic compounds as well find
application as potential drugs, because multi-functional groups are present. Thiazoles are very
essential building are block in medicinal chemistry, different natural product such has
epothilone. The imin group –N=CH- characterizes the Schiff bases. The is explaining the
transformation and racemizarion mechanism in the bio inorganic chemistry is well has improve
in the concentration on the Schiff bases. The studied of glycine and phenylalanine Schiff based
ligands applied in the antifngal activity against fungi, C. albicans. Antifungal strengths of the
matched controller medicines Fluconazole was perceived to be superior to the consistent
compounds, showing MIC values of 0.5 mg/mL, while its developments were minus active with
MIC value 128-256 mg/mL. The manufactured compounds were separated in vitro for their
antimicrobial activities and nearly of them revealed adequate to good antimicrobial activities
beside the certain C. albicans12.
Schiff bases ligands, formed the by condensation of 2.6-diacyplyridine or the 2,6-
diformylpyridin and appropariate polyamines, which is the utilize the templating capability of
the different metal ions to direct the synthetic pathway. The reduction of the cyclic Schiff bases
to their related amine derivatives is also considered since this leads to more flexible ligands
capable of structural elaboration through donor group. Attention is mainly paid to the synthetic
and structural aspects of the resulting metal complexes, particularly to the role of the
coordination preference of the different metal ion in directing the synthesis totally or
preferentially toward mono-di- or poly-nuclear entities. The preparation of functionalized
ligands, containing to pendant arms, capable of promoting rapid complexation and
decomplexation and their use in selective metal transportation and separation are also paid
attention to furthermore13.
Hydroxyaldehydes are common compounds, with the class of carbohydrates being included in
this type of compound. Pyrolysis of carbohydrates is discussed separately in Chapter 11. Even
excluding carbohydrates, numerous other compounds have both the OH and the CHO
functionalities. These functionalities can be positioned on the same carbon (e.g.,
glycolaldehyde), or they can be in β, γ, etc., position. Glycolaldehyde (or hydroxyacetaldehyde)
is not stable to heating and, when kept around 100°C for several hours, undergoes a
condensation13.
Figure 1.1 Condensation reaction of aldehyde.
Vanillin is a member of the class of benzaldehydes carrying methoxy and hydroxyl substituents
at positions 3 and 4 respectively. It has a role as a plant metabolite, a flavouring agent, an
antioxidant and an anticonvulsant. It is a member of phenols, a monomethoxybenzene and a
member of benzaldehydes. Vanillin (3-methoxy-4-hydroxybenzaldehyde) is a white crystalline
compound that can be isolated from vanilla plant (Vanilla planifola), the highest concentration of
this compound being in the seeds. It is one of most commonly used flavorings and perfuming
agents worldwide in the food and cosmetic industries, and because of its high volume of
consumption, today most vanillin is produced by chemical synthesis. Vanillin is a polyfunctional
compound with an aromatic ring bonded to an aldehyde group, -OH phenolic, and a methoxy
group13.
Figure 1.2 Structure of 3-methoxy-4-hydroxybenzaldehyde.
Nies et al., 2013 synthesized 3,5-difluoro-4-hydroxybenzaldehyd was essentially performed as
originally described, we found that the use of 4-dimethylaminopyridine as a catalyst was crucial
for achieving high yield
Figure 1.3 Structure of 3,5-difluoro-4-hydroxybenzaldehyd.
4-Hydroxybenzaldehyde is as shown in figure 1.3. one of the
three isomers of hydroxybenzaldehyde isolated from Gastrodia elata Blume (Orchidaceae), has
been involved in the beneficial effect on insulin resistance in a type 2 diabetic animal model (rats
fed a high-fat diet). The mechanism of action of this compound includes the potentiation of
glucose uptake demonstrated in 3T3-L1 adipocytes as well as the stimulation of glucose
metabolism and the inhibition of hepatic glucose production. Moreover, G. elata Blume water
extract mainly as a result of the action of 4-hydroxybenzaldehyde14.
Figure 1.4 Structure of 4-Hydroxybenzaldehyde
Chapter-2 EXPERIMENTAL
2.1. General
All chemicals were of most elevated available and used as provided. 2-
bromrobenzaldehyde and pyrrole-2-carbaldehyde were purchased from Sigma Aldrich; acetic
acid was obtained from Merck and utilized without advance purification. Distillation is used to
dried fluid amines over KOH and place away under nitrogen air over KOH pellets. Dry solvents
like n-hexane, chloroform, methanol, THF and DCM were distilled utilizing standard methods.
Needles and glassware were flame dried instantly anterior to place or use in an oven (150-160
°C) 2-3 hours at least and allowed to cool in desiccators or under reduced pressure. Liquid
reagents, solvents or solutions w ere used via syringe or tube with rub Wiesner, J., Ortmann, R.,
Jomaa, H., & Schlitzer, M. (2003). New antimalarial drugs. Angewandte Chemie International
Edition, 42(43), 5274-5293ber septa. While schlenk type adapters used to add solid reagents.
TLC (Kieselgel 60 F254) is used (Merck) to monitor all the Reactions, ethyl acetate/n-Hexane
(3:7) was used as eluent. TLC chromatograms were checked under UV light (lmax 254 and
365nm).
To concentrate reaction mixture Buchi rotary evaporator (bath temperature up to 45 °C) were
used under reduced pressure using both at a pressure of either 15 mm 0.1 mm of Hg (oil pump)
or Hg (diaphragm pump), as correct and a high vacuum line at RT. Using digital melting point
(Gallenkamp apparatus) melting points (M.P) were observed in Celsius scale (°C) and are
uncorrected.
2.2. solid phase Synthesis of Schiff bases
For the synthesis of Schiff bases, 2-bromrobenzaldehyde and pyrrole-2-
carbaldehyde were used.
2.3, General Procedure
2-bromrobenzaldehyde (0.38 mg) and substituted aniline (0.3ml) were mixed in a mortar.
To the mixture H2SO4, sodium bicarbonate or Acetic acid (0.5 mL) was added. The reaction
mixture was ground together in a mortar using pestle to generate a colored tacky solid within 30-
60 min. The reaction proceeds exothermically (indicated by rise in temperature of 5- 50C). After
the reaction (TLC), water (10 mL) was added, solid separates out. The separated solid was
filtered, washed with cold water and crystallized from ethyl alcohol.
2.4 Synthesis of 1-(2-bromophenyl)-N-(2-chloro-4 methylphenyl) methanimine (SB-H)
The compound 1-(2-bromophenyl)-N-(2-chloro-4 methylphenyl) methanimine (SB-H)
was synthesized from 2-brombenzaldehyde and 2-chloro 4-methyl aniline by the general
procedures as described above. The compound was recrystallized from ethyl alcohol.
Yield: 73%. White crystalline solid. M.P = 89-96 °C. Rf = 0.73 (ethyl acetate: hexane, 3:7)
fiure no 1.5 Chemical formula of 1-(2-bromophenyl)-N-(2-chloro-4 methylphenyl) methanimine
2.5 Synthesis of N-(2-chloro-4-methylphenyl)-1-(1H-pyrrol-2-yl) methanimine (SB-I)
The compound N-(2-chloro-4-methylphenyl)-1-(1H-pyrrol-2-yl) methenamine (SB-I) was
prepared from 2-pyrrole carbaldehyde and 2-choloro 4-methyl aniline, following the general
procedure as described above.
figure 1.6 Yield: 65%. Whit ecrystalline solid. M.P = 105-112°C. Rf = 0.66 (ethyl acetate: n.
hexane, 3:7
Chapter -3
RESULTS AND DISCUSSION
Due to the importance of Schiff bases in synthetic organic chemistry in recent years, we
designed to synthesize some new azomethine or Schiff bases. In our research work, we have
selected 2-bromobenzaldehyde and 2-pyrrole carbaldehyde. Schiff bases acylation started by
attack at nitrogen atom and prompts net addition of the acylating agent to the carbon-nitrogen
double bond.
3.1 Synthesis of Schiff bases
Different methods have been reported for the synthesis of Schiff bases, in our research
work, we have used the solid-phase method. 2-bromobenzaldehyde and 2-pyrrole carbaldehyde
(0.45g, 3 mmol) and 2-chloro,4-methyl aniline (0.3ml, 3 mmol) were mixed in a mortar. To the
mixture Acetic acid (0.5mL) was added. The reaction mixture was ground together in a mortar
using pestle to generate pale yellow colored tacky solid within 15-20 min. The reaction proceeds
exothermically (indicated by rise in temperature of 5-10 0C). After the reaction (TLC), water (10
mL) was added, solid separates out. The separated solid was filtered, washed with cold water and
crystallized from ethyl alcohol. (Scheme 1)
Scheme 1: synthesis of Schiff bases (SB-H, SB-I)
The time of reaction, nature of catalyst and yields of the products by two different methods is
tabulated in table 4.1.
Table 5.1 Comparison Of Different Conditions Of Both Reactions
S no aldehyde Amine Yield % time of Catalyst Ph
reaction
1 2- 2-chloro 56 (A) (A) H2SO4 4-5
bromoben 4-methyl 1Hour
73 (B) Glacial
zaldehyde aniline
(B) 4 acetic acid
Hour
2 2-pyrrole 2-chloro 60 (A) 30 (A) H2SO4 4-6
carbaldeh 4-methyl minutes
65 (B) Glacial
yde aniline
(B) 2 acetic acid
Hour
All the compounds were purified by recrystallization and were further identified by their
physical data like melting point, Rf value.
3.2 Synthesis of 1-(2-bromophenyl)-N-(2-chloro-4 methylphenyl) methanimine (SB-H)
The compound Synthesis of 1-(2-bromophenyl)-N-(2-chloro-4 methylphenyl)
methanimine (SB-H) was synthesized from. 2-bromobenzaldehyde and 2-chloro,4-methyl
aniline (scheme 1)
3.3 Characterization of Synthesis of 1-(2-bromophenyl)-N-(2-chloro-4 methylphenyl)
methanimine (SB-H)
The synthesis of the 2 Synthesis of 1-(2-bromophenyl)-N-(2-chloro-4 methylphenyl)
methanimine (SB-H) was confirmed by its melting point. The percentage yield, melting point
and Rf value is tabulated in table 5.2.
Table 5.2: Physical data of 2-methoxy-4-((4-nitrophenylimino) methyl) phenol (SB-i)
Physical
Melting point (C) Yield (%) Rf＊
appearance
Greenish solid 89-96 56% (A), 73% (B) 0.73
＊
(ethyl acetate: n. hexane 3:7)
3.4 Synthesis of N-(2-chloro-4-methylphenyl)-1-(1H-pyrrol-2-yl) methanimine (SB-I)
The compound Synthesis of N-(2-chloro-4-methylphenyl)-1-(1H-pyrrol-2-yl)
methanimine (SB-I) was synthesized by the reaction of 2-pyrrole carbaldehyde and 2-chloro,4-
methyl aniline.
3.5 Characterization of N-(2-chloro-4-methylphenyl)-1-(1H-pyrrol-2-yl) methanimine (SB-I)
The synthesis of (SB-I) was identified by its melting point. The percentage yield, melting
point and Rf value is tabulated in table 5.3
Table 5.3: Physical data of 2-methoxy-5-((phenylimino)methyl) phenol (SB-B)
Physical appearance Melting point (C) Yield (%) Rf＊
Yellow solid 105-112 60 % (A), 65% (B) 0.66
sy
＊
(ethyl acetate: n. hexane 3:7)
Conclusion
In conclusion, novel Schiff bases like synthysis of 1-(2-bromophenyl)- N-2-chloro-4-
methyl phenyl methaimine (SB-H) and synthysis of N-(2-chloro-4- methylphenyl)-1-1H-pyrrol-
2-ylmethaimine(SB-I)were synthesized by solid – phase procedur-.
The compounds werw obtained in high yield and short reaction time (A)1 hour 30 minutes B) 4
hour.
All the synthesized schillf bases were identified by there physical data like colour, melting point
and Rf value .
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